1. Field of the Invention
The present invention relates to compositions for the treatment of preterm infants. In particular the present invention relates to pulmonary surfactant compositions which are useful for reducing the pulmonary oxidative damage and the risk of developing bronchopulmonary dysplasia in preterm infants. The present invention further relates to methods for treating and/or preventing certain conditions by administering such a pulmonary surfactant composition.
2. Discussion of the Background
The human lung is composed of a large number of small air sacs, called alveoli, in which gases are exchanged between the blood and the air spaces of the lungs. In healthy individuals, this exchange is mediated by the presence of a protein-containing surfactant complex that prevents the lungs from collapsing at the end of expiration.
The lung surfactant complex is composed primarily of lipid and contains minor amounts of various proteins. An absence of adequate levels of this complex results in malfunction of the lungs. This syndrome is called Respiratory Distress Syndrome (RDS) and it commonly affects preterm infants.
The mainstay of the treatment of RDS is replacement therapy with exogenous pulmonary surfactant preparations extracted from animal lungs, known as modified natural surfactants. For instance, modified natural surfactants used in the clinical practice are poractant alfa derived from porcine lung, and sold under the trademark of CUROSURF®, beractant (SURFACTEN® or SURVANTA®) and bovactant (ALVEOFACT®), both derived from bovine lung, and calfactant derived form calf lung (INFASURF®).
Exogenous pulmonary surfactants are currently administered by endotracheal instillation as a suspension in a saline aqueous solution to intubated pre-term infants kept under mechanical ventilation with oxygen.
Although said therapy has greatly increased postnatal survival, children that survive RDS have a high risk of developing bronchopulmonary dysplasia (BPD), a complication that impedes lung development and ultimately leads to impaired breathing. Evidence indicates that pulmonary inflammation and oxidative injury of lung tissues play an important role in the pathogenesis of BPD. Furthermore, inflammation and oxidative stress contribute to surfactant inactivation through the alveolar transudation of plasma proteins and cells and the direct action of free radicals.
The risk of developing BPD in infants affected by RDS can be reduced by administering a corticosteroid within a few weeks postnatally. However, the effectiveness of postnatal corticosteroid administration is offset by possible adverse systemic effects, e.g., hypertension, hyperglycemia, gastrointestinal complications, and neurodevelopmental disability.
As an alternative to systemic administration, delivery of corticosteroid by inhalation or intracheal instillation has been proposed. For example, Yeh et al. (Pediatrics 2008, 121(5), e1310-e1318) proposed the intratracheal instillation of budesonide using the surfactant Survanta® as a carrier. However, as reported in US 2007/0225233, the relevant delivery procedure suffers from some drawbacks in terms of compliance as it foresees the administration of the medicament in four aliquots, each aliquot being administered in different and rather complicated positions of the infant.
In view of the above considerations, there is still a need to develop a more compliant medicament able of effectively reducing the markers of pulmonary inflammation and oxidative stress, and hence the risk of BPD in infants suffering from RDS.
In particular, since mechanical ventilation is an invasive procedure which has been recognized to contribute to the development of BPD, it would be of particular advantage to provide a medicament that may also be effectively administered by methods avoiding said respiratory support.